DESCRIPTION: The overall objective of this renewal proposal is to determine the molecular basis of hepatocyte growth factor (HGF) gene transcription and its function in normal tissue development and tumorigenesis. The first specific aim is to functionally map the regulatory DNA elements in the HGF gene promoter and to characterize the cognate binding proteins that govern HGF gene transcription in a cell-type specific manner in the liver. The second specific aim is to use HGF overexpressing transgenic mice to unravel the mechanisms by which HGF contributes to liver growth and neoplastic transformation. The third specific aim is to produce a transgenic mouse that expresses a recombinant HGF antagonist in the liver to study its effects on normal liver growth and differentiation and hepatocarcinogenesis.